Language and arithmetic--a study using the intracarotid amobarbital procedure

The intracarotid amobarbital procedure is used as a standard procedure in presurgical evaluation to assess hemispheric lateralization of language and memory, but has not been applied to investigate numerical processing. Patients with medically intractable epilepsy (n=20) were consecutively recruited during a presurgical evaluation programme. All 14 patients with left-lateralized language showed better arithmetic performance with the left hemisphere (intracarotid amobarbital procedure right), while five out of six patients with bilateral or right-hemispheric language representation showed better performance with the right hemisphere (intracarotid amobarbital procedure left). Furthermore, in patients with left-lateralized language, an interaction between intracarotid amobarbital procedure and type of arithmetic operation was found. The study suggests a close association between language lateralization and hemispheric specialization for arithmetic processing.     

Unexpected right hemisphere language representation identified by the intracarotid amobarbital procedure in right-handed epilepsy surgery candidates

The intracarotid amobarbital procedure (IAP) is used for language lateralization in the presurgical evaluation for intractable epilepsy. Some epilepsy surgical centers forgo IAP for right temporal lobectomies in right-handed patients with no personal/family history of left-handedness, implying that right hemisphere language representation does not occur in these patients. To test this hypothesis, a retrospective analysis was performed on 156 consecutive epilepsy surgery candidates who underwent IAP. Of the 156 candidates, 122 were right-handed, and 55 of the 122 demonstrated right hemisphere seizure focus. Right hemisphere language representation was found in 22 of 55 patients, with two demonstrating significant right hemisphere language despite a right hemisphere seizure focus and no family history of left-handedness. Only 1 of 156 patients undergoing IAP experienced permanent neurological complications. Although relatively uncommon, right hemisphere language representation may occur more frequently than complications from cerebral angiography and, therefore, presurgical IAP is recommended for all epilepsy surgery candidates regardless of handedness to minimize the risk of severe language decline.     

Right cerebral specialization for tactile attention as evidenced by intracarotid sodium amytal

Although several components of neglect syndrome have been reported to occur more frequently following right cerebral lesions, a right cerebral predominance for directed tactile attention has not been demonstrated. The intracarotid sodium amytal procedure (ISA, or Wada test) offers the opportunity to investigate differential effects for symmetric acute dysfunction of each cerebral hemisphere in each subject. In the present study, 18 patients undergoing preoperative evaluation for epilepsy surgery were trained in a nonverbal task of tactile attention. Left/right mean ISA dosages and left/right tactile test times postinjection were matched. Results revealed more correct responses following left ISA, and greater tactile inattention with more extinction-type responses following right ISA. No effect of seizure focus, sex, order of injection, or dosage was present. The finding that tactile inattention occurs more frequently with right cerebral dysfunction is consistent with right cerebral dominance for scanning attentional mechanisms directed at the external milieu.     

Crossed apraxia: implications for handedness.

Liepmann posited that right hand preference relates to left hemisphere dominance for learned skilled movements. Limb apraxia, impairment of skilled movement, typically occurs in individuals with left hemisphere (LH) lesions. The occurrence of apraxia in right-handed individuals following right-hemisphere lesions appears to refute Liepmann's hypothesis. We studied the apraxia of a right-handed man, RF, following a right frontal lesion to determine whether his apraxia paralleled the apraxia seen following LH lesions. Results of behavioral testing indicated that, like individuals with apraxia following left frontal lesions, RF was better at gesture recognition than gesture production which was significantly impaired across tasks. Kinematic motion analyses of movement linearity, planarity, and the coupling of temporospatial aspects of movements substantiated the parallel impairments in RF and patients with LH apraxia. The impairment seen in our patient with crossed apraxia provides evidence for the fractionation of systems underlying hand preference and skilled movement.     

Right hemisphere language mapping in patients with bilateral language

PURPOSE: The configuration of language cortex in the dominant left hemisphere has been well described in the literature. However, language representation in the right hemisphere, particularly in patients with some degree of bilateral language, remains unclear. Herein, we report six patients who underwent electrocortical stimulation (ECS) for language mapping following implantation of a right subdural electrode array (SEA). METHODS: The medical records of six bilateral language patients with right SEA implantation at the Minnesota Epilepsy Group between January 1996 and July 2004 were retrospectively reviewed. Language lateralization was based on the results of the intracarotid amobarbital procedure performed preoperatively. Anatomical localization of the SEA for each patient was verified using colored photographs of the cortical surface before and after SEA placement and by review of MRI scans taken with the SEA in place. Frontal and temporal language areas were identified by errors in any language modality including automatic speech, reading, naming, repetition, and comprehension during ECS. RESULTS: Language maps revealed the presence of frontal and/or temporal language areas analogous to the classic essential language areas of the dominant left hemisphere in four of six patients. One patient had a widespread distribution of single-language-error sites over the right temporal lobe. One patient had a silent language map. CONCLUSION: Our results identified the presence of language cortex in the right hemisphere in five of six patients classified with bilateral language based on intracarotid amobarbital procedure. These areas are assumed to be accessory language zones in relation to the left hemisphere. Further exploratory studies are needed to evaluate their clinical significance.     

Affective self-report during the intracarotid sodium amobarbital test: group differences.

Emotional reactions are sometimes observed during the intracarotid sodium amobarbital test. For instance, euphoric/indifference reactions can be seen during right hemisphere inactivation and catastrophic reactions may accompany left hemisphere inactivation. Less dramatic changes can also be detected in affective self-report during left and right hemisphere amobarbital tests, with more negative affect reported during left hemisphere inactivation and either neutral or mildly positive affective states reported during right hemisphere inactivation. The current study not only replicated this effect, but in addition, found significant group differences. The first group (right way) showed a pattern of affective self-report during left and right amobarbital tests entirely consistent with prior findings, while a second group (wrong way) showed results that behaved in a diametrically opposite fashion. A third group (no change) showed little, if any, difference in affective self-report during left and right amobarbital tests. The major factor distinguishing the wrong way group from the other two appeared to be an asymmetrical distribution of left and right temporal lobe lesions in the former group. In contrast, the factor differentiating the right way group from the no change group appeared to be the relative degree of left hemisphere inactivation during the left hemisphere amobarbital test. The results are discussed not only in terms of their impact on theories of cerebral lateralization for emotion, but also in terms of methodological issues in this field.     

Heart rate and heart rate variability changes in the intracarotid sodium amobarbital test

PURPOSE: Changes in heart rate and heart rate variability have been found in prior studies performed during the intracarotid sodium amobarbital (ISA) test. However, these results are not entirely consistent with current models of differential cerebral involvement in the modulation of the heart. This study was designed to re-investigate this topic with a larger N than has heretofore been used. METHODS: The electrocardiogram was recorded during left and right ISAs in 73 subjects. Raw heart rate and heart rate variability were calculated. RESULTS: Raw heart rate increased during inactivation of either hemisphere, but more so for the right hemisphere. Heart rate variability changes consistent with decreasing parasympathetic tone also were found to occur during either ISA, but to a significant degree, only during right ISA. CONCLUSIONS: The right hemisphere appears to have a greater role in cerebral regulation of cardiac function, perhaps by virtue of the modification of parasympathetic effects.     

Neural correlates of verbal semantic memory in patients with temporal lobe epilepsy

Functional imaging data suggest that the core network engaged in verbal semantic memory (SM) processing encompasses frontal and temporal lobe structures, with a strong left lateralization in normal right handers. The impact of long term temporal lobe epilepsy (TLE) on this network has only partly been elucidated. We studied verbal SM in 50 patients with chronic, intractable TLE (left TLE=26, right TLE=24) and 35 right handed normal controls using a verbal fMRI semantic decision paradigm. All patients had language lateralized to the left hemisphere, as verified by the intracarotid amobarbital procedure. Within and between group analyses showed remarkable, group-specific activation profiles. The control group activated frontal and temporal areas bilaterally, with a strong left predominance. Left TLE patients showed a shift of activations of left frontal and medial temporal areas to homologous regions in the right hemisphere. Furthermore, left TLE subjects utilized subcortical structures such as the thalamus and putamen to accomplish the verbal SM task. Contrastively, the activation pattern of right TLE patients resembled that of normal controls, but exhibited "hypofrontality" with a shift from frontal to posterior regions in the temporal, parietal and occipital lobe. Our results show that chronic epileptic activity originating from temporal seizure foci is associated with an alteration of neural circuits which support semantic language processing and that side of seizure focus has a specific impact on the resulting activation network. These findings presumably result from morphological changes and from functional reorganization which are both inherent to chronic TLE.     

Right Hemisphere Language Dominance in a Right-Handed Patient with Late-Onset Seizures

Right hemisphere language dominance is rare in right-handed individuals and usually the result of language transfer associated with early left hemisphere pathology. We studied a 33-year-old right-handed man, with a normal MRI scan, who developed left frontal lobe seizures at age 15 years. Language lateralization testing by intracarotid amobarbital injection and dichotic listening showed the patient to be strongly right hemisphere language dominant. The clinical features of this patient do not fit the profile of pathology-induced language transfer, but instead suggest that he was right hemisphere language dominant before developing seizures. This case underscores the importance of language lateralization testing in patients who are candidates for seizure surgery, even if they are strongly right-handed and have late-onset seizures, features usually associated with left hemisphere language dominance. One implication is that the incidence of right hemisphere language dominance in the right-handed population may be underestimated.     

Unilateral cerebral inactivation produces differential left/right heart rate responses

We studied heart rate following unilateral hemispheric inactivation by intracarotid amobarbital in 25 patients undergoing preoperative evaluation for epilepsy surgery. Heart rate increased after left hemisphere inactivation, but decreased following right hemisphere inactivation. The results are consistent with differential left/right cerebral hemispheric effects on autonomic function, and appear related to functional and anatomic asymmetries in both the central and peripheral nervous systems.     

Intracarotid amobarbital (Wada) test for language dominance: correlation with results of cortical stimulation

Eighty-eight patients had bilateral intracarotid amobarbital (Wada) testing to determine hemispheric dominance for language in preparation for epilepsy surgery, as well as unilateral extraoperative cortical electrical stimulation using subdural electrode arrays. In none of the patients with left dominance by Wada testing were language areas found with right-sided stimulation, but two patients with right dominance by Wada testing had language areas mapped on the left side. These findings suggest that left dominance by Wada testing is strong evidence for exclusive lateralization of language function in the left hemisphere, but there is concern about the ability of the Wada test to exclude the possibility of some left-sided language function despite apparent right-sided dominance. Patients with left dominance on Wada testing do not need cortical stimulation before extensive right temporal lobectomy, but we believe that patients with right or bilateral dominance on Wada testing should have cortical stimulation for localization of language areas if extensive left or right temporal or frontal resection is planned.     

Time Perception Following Unilateral Amobarbital Injection in Patients with Temporal Lobe Epilepsy

Estimates of elapsed time were obtained from 53 patients with unilateral temporal lobe epilepsy (Left TLE = 27; Right TLE = 26) following Wada (intracarotid amobarbital) assessment. After resolution of drug effects, patients were asked to estimate how much time had passed since amobarbital administration. Estimates were also obtained from 24 healthy control subjects using the same cognitive tasks over a similar time frame. Elapsed time was significantly underestimated by both left and right TLE groups following right hemisphere injection. In addition, there was an interaction effect involving patient group, side of injection, and sequence of injection. Left TLE patients, consistent with normal controls, made more accurate time estimates when they could anticipate the estimation task following the second amobarbital administration. More accurate time estimates, however, occurred only when left hemisphere injection was second in sequence. In contrast, right TLE patients did not improve regardless of the order of injection. These results suggest that right hemisphere function plays a critical role in the accuracy of time estimations of intermediate temporal duration and that interhemispheric interaction may be required to make accurate retrospective temporal judgments. These findings are discussed in the context of the growing evidence for a right-hemispheric attentional network.     

Verbal and figural fluency in patients with mass lesions of the left or right frontal lobes.

Impaired verbal and figural fluency has been shown to be associated with frontal lobe dysfunction. Jones-Gotman and Milner (1977) demonstrated a double dissociation between verbal and nonverbal fluency in a small sample of patients with frontal lesions of the left or right hemisphere. The present study has examined verbal and nonverbal fluency in 25 healthy participants and 95 patients with mass lesions of the left or right frontal lobes. In comparison with healthy participants, verbal fluency was reduced in patients with frontal lesions of the left hemisphere. Patients with right-sided lesions did not differ from either the control group or from the patients with left-sided frontal mass lesions. In the figural fluency task, the performance of the groups did not differ. The finding that patients with left frontal lesions produced fewer words than healthy participants suggests an association between left frontal lobe pathology and reduced verbal fluency. The results do not support the hypothesis of a double dissociation between verbal/figural fluency and the side of lesion within the frontal lobes.     

Verbal and Figural Fluency in Patients with Mass Lesions of the Left or Right Frontal Lobes

Impaired verbal and figural fluency has been shown to be associated with frontal lobe dysfunction. Jones-Gotman and Milner (1977) demonstrated a double dissociation between verbal and nonverbal fluency in a small sample of patients with frontal lesions of the left or right hemisphere. The present study has examined verbal and nonverbal fluency in 25 healthy participants and 95 patients with mass lesions of the left or right frontal lobes. In comparison with healthy participants, verbal fluency was reduced in patients with frontal lesions of the left hemisphere. Patients with right-sided lesions did not differ from either the control group or from the patients with left-sided frontal mass lesions. In the figural fluency task, the performance of the groups did not differ. The finding that patients with left frontal lesions produced fewer words than healthy paticipants suggests an association between left frontal lobe pathology and reduced verbal fluency. The results do not support the hypothesis of a double dissociation between verbal/figural fluency and the side of lesion within the frontal lobes.     

Neural correlates of verbal semantic memory in patients with temporal lobe epilepsy

Functional imaging data suggest that the core network engaged in verbal semantic memory (SM) processing encompasses frontal and temporal lobe structures, with a strong left lateralization in normal right handers. The impact of long term temporal lobe epilepsy (TLE) on this network has only partly been elucidated. We studied verbal SM in 50 patients with chronic, intractable TLE (left TLE = 26, right TLE = 24) and 35 right handed normal controls using a verbal fMRI semantic decision paradigm. All patients had language lateralized to the left hemisphere, as verified by the intracarotid amobarbital procedure. Within and between group analyses showed remarkable, group-specific activation profiles. The control group activated frontal and temporal areas bilaterally, with a strong left predominance. Left TLE patients showed a shift of activations of left frontal and medial temporal areas to homologous regions in the right hemisphere. Furthermore, left TLE subjects utilized subcortical structures such as the thalamus and putamen to accomplish the verbal SM task. Contrastively, the activation pattern of right TLE patients resembled that of normal controls, but exhibited ‘hypofrontality’ with a shift from frontal to posterior regions in the temporal, parietal and occipital lobe. Our results show that chronic epileptic activity originating from temporal seizure foci is associated with an alteration of neural circuits which support semantic language processing and that side of seizure focus has a specific impact on the resulting activation network. These findings presumably result from morphological changes and from functional reorganization which are both inherent to chronic TLE.     

Linguistic perseveration in dominant-side intracarotid amobarbital tests.

148 patients with medically intractable complex-partial seizures received bilateral intracarotid amobarbital tests. In 21 patients (14.2%), there were inappropriate responses (intrusions: N = 10; perseverations: N = 11) to a series repetition task (counting backwards) given immediately before amobarbital injection. Five cases from the perseveration subgroup are discussed in detail. In these patients, linguistic perseveration occurred with left-sided amobarbital injection, although they were all found to have left hemispheric speech dominance according to language testing during the amobarbital procedure. It is argued that these perseverations are best explained as a right hemispheric continuation of a speech motor program previously initiated by the left hemisphere.     

Integration of Perceptual and Mnemonic Dysfunction: Sensory Auras Are Associated with Left Hemispheric Memory Impairment

Memory function during the intracarotid amobarbital test was studied to test the hypothesis that left hemisphere memory impairment is associated with sensory auras. In a series of 37 patients undergoing preoperative evaluation for epilepsy surgery, the quantitative memory scores during amobarbital inactivation of right and left hemisphere were analyzed for correlation with habitual epileptic auras classified as either (a) experiential, forced emotion, or whole-body dysphoria or (b) sensory hallucinations and/or illusions or localized dysesthesias. The left hemispheric memory score impairment was significantly worse in association with auras classified as sensory hallucinations and/or illusions or localized dysesthesias compared with auras classified as experiential, forced emotion, or whole-body dysphoria (P < 0.05). This finding may assist in predicting left-sided hemispheric memory dysfunction in patients with seizures beginning as auras involving sensory material. The results suggest an integration of perceptual and mnemonic dysfunction in which sensory auras are associated with left hemispheric memory impairment.     

Language lateralization in temporal lobe epilepsy: a comparison between fMRI and the Wada Test

PURPOSE: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI-based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT). METHODS: To establish the power of language fMRI to detect language lateralization during presurgical assessment, we compared the findings of a semantic decision paradigm with the results of a standard IAT in 68 patients with chronic intractable right and left temporal lobe epilepsy (rTLE, n=28; lTLE, n=40) who consecutively underwent a presurgical evaluation program. The patient group also included 14 (20.6%) subjects with atypical (bilateral or right hemisphere) speech. Four raters used a visual analysis procedure to determine the laterality of speech-related activation individually for each patient. RESULTS: Overall congruence between fMRI-based laterality and the laterality quotient of the IAT was 89.3% in rTLE and 72.5% in lTLE patients. Concordance was best in rTLE patients with left speech. In lTLE patients, language fMRI identified atypical, right hemisphere speech dominance in every case, but missed left hemisphere speech dominance in 17.2%. Frontal activations had higher concordance with the IAT than did activations in temporoparietal or combined regions of interest (ROIs). Because of methodologic problems, recognition of bilateral speech was difficult. CONCLUSIONS: These data provide evidence that language fMRI as used in the present study has limited correlation with the IAT, especially in patients with lTLE and with mixed speech dominance. Further refinements regarding the paradigms and analysis procedures will be needed to improve the contribution of language fMRI for presurgical assessment.     

Mechanisms of recovery from aphasia: evidence from serial xenon 133 cerebral blood flow studies

In 21 patients who suffered aphasia resulting from left hemisphere ischemic infarction, the xenon 133 inhalation cerebral blood flow technique was used to measure cerebral blood flow within 3 months and 5 to 12 months after stroke. In addition to baseline measurements, cerebral blood flow measurements were also carried out while the patients were performing purposeful listening. In patients with incomplete recovery of comprehension and left posterior temporal-inferior parietal lesions, greater cerebral blood flow occurred with listening in the right inferior frontal region in the late studies than in the early studies. In patients with nearly complete recovery of comprehension and without left posterior temporal-inferior parietal lesions, early listening studies showed diffuse right hemisphere increases in cerebral blood flow. Later listening studies in this latter patient group showed greater cerebral blood flow in the left posterior temporal-inferior parietal region. The study provides evidence for participation of the right hemisphere in language comprehension in recovering aphasics, and for later return of function in left hemisphere regions that may have been functionally impaired early during recovery.     

Longitudinal study of regional cerebral blood flow changes in depression after stroke.

BACKGROUND: We studied 60 patients longitudinally to examine relations between regional cerebral blood flow and depressive states after stroke. METHODS: Poststroke depressive states were assessed by the Zung Self-Rating Depression Scale (SDS). Regional cerebral blood flow was measured using the 133xenon inhalation method with patients in the resting state on the same day as the SDS assessment. All patients were followed for an average of 14 months after the initial assessment. RESULTS: Severity of depression was inversely correlated with regional cerebral blood flow values in the parieto-occipital regions of the right hemisphere and in the anterior temporal region of the left hemisphere at the initial evaluation. Patients with lesions in left frontal or right parieto-occipital regions were more depressive in comparison with those with other brain lesions. Follow-up study showed significant inverse correlations between changes in SDS score and changes in regional cerebral blood flow at all scalp sites. Furthermore, higher inverse correlations were observed at specific brain regions in each hemisphere, including the parietal and parieto-occipital regions of the right hemisphere and the anterior temporal and inferior frontal regions of the left hemisphere. This relation was independent of recovery from neurological deficits. CONCLUSIONS: These results suggest that dysfunction of specific cortical and subcortical regions in both hemispheres asymmetrically contributes to depressive state after stroke.